Rapid non-genomic actions of 25(OH)D3: state of the art

Over recent years, the secosteroid hormone calcitriol (1α,25(OH)2D3) has been attracting growing attention due to its essential role in calcium absorption and bone mineralization. This hormone elicits these functions through genomic and non-genomic mechanisms. In the former case, the interaction of 1α,25(OH)2D3 with vitamin D receptor (VDR) results in the transcription of genes involved in the regulation of calcium homeostasis. Compared with their genomic counterparts, non-transcriptional effects, on the other hand, occur rapidly and are not subject to the effects of transcription and protein synthesis inhibitors; they have also been shown to be responsible for the multiple actions of vitamin D. The direct precursor metabolite of 1α,25(OH)2D3, calcifediol (25(OH)D3), which also exhibits anti-proliferative and gene regulatory properties, was recently described as an agonistic ligand of VDR, albeit with lower affinity than 1α,25(OH)2D3. This mini-review attempts to offer an overview of the non-genomic actions of calcifediol and the possible mechanisms underlying the generation of these rapid responses. Insights into the rapid non-genomic mechanisms of 25(OH)D3 could help to increase knowledge of the vitamin D endocrine system, and thus result in the identification of novel therapeutic strategies able to regulate non-genomic actions, which could prove crucial in 25(OH)D3 deficiency-related disorders.

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